Proposed model of RNL function in immunity.
Upon an infection of a plant cell by a pathogen, the first (early) response induced is PTI, irrespective of whether it is an avirulent or virulent pathogen. Thus, basal resistance and ETI happen in cells in which PTI signaling was already initiated and in some or the other way counteracted by effectors and other virulence molecules. Therefore, we propose that RNL function in immunity has to be considered as being part of a complex immune response network depicted in this proposed model. (1) Basal resistance (grey arrows) is initiated by the recognition of PAMPs by cell surface-localized PRRs. (2) PRR-triggered responses lead to the accumulation of SA and induction of SA responses, which requires RNLs . (3) Pathogen-derived (virulence) effectors and the JA analog coronatine counteract PRR- and RNL-induced immunity and SA responses, thereby causing the so called (first) ETS. (4) Many pathogens, especially pathogenic bacteria, have effectors that can be recognized by some sensor TNL or CNLs and only induce a “weak remnant” ETI response  during basal resistance. This most likely leads to the activation of RNLs and can explain their requirement for basal resistance (see Fig 3). (5) It is possible that the aforementioned “weak” recognition and sensor NLR activation is also targeted by other effectors, causing the second ETS . (6) RNLs are fully required for TNL-mediated immunity (black arrows) with some structural preferences for either ADR1s or NRG1s. After being activated by TNLs, RNLs act as CNLs to trigger strong and lasting defense activation as well as HR. ADR1s and NRG1s seem partially specialized in defense and HR, respectively, although the sub-functionalization is not strict. For example, ADR1s are specifically required for RPP4 signaling, while NRG1s are specifically required for RPS4-induced HR. (7) In addition, RNLs are involved but not required for CNL-triggered defense gene expression and HR (red arrows), further suggesting that RNLs act not directly downstream but in parallel with CNLs. If the sensor CNL is able to trigger a strong ETI by itself, the RNL involvement does not translate into requirement for proper disease resistance (e.g., RPM1 or ZAR1 ETI). Grey arrows indicate basal resistance (and PTI) signaling; black arrows indicate TNL-mediated ETI, and red arrows indicate CNL-mediated ETI signaling. Structural formula of coronatine was downloaded from Wikipedia (https://en.wikipedia.org/wiki/Coronatine). CNL, coiled-coil domain-containing nucleotide-binding leucine-rich repeat receptor; ETI, effector-triggered immunity; ETS, effector-triggered susceptibility; HR, hypersensitive response; JA, jasmonic acid; NLR, nucleotide-binding leucine-rich repeat receptor; PAMP, pathogen-associated molecular pattern; PRR, PAMP recognition receptor; PTI, pattern-triggered immunity; SA, salicylic acid; SAR, systemic acquired resistance; TNL, TIR domain-containing NLR.